Characterization of H2O2-induced acute apoptosis in cultured neural stem/progenitor cells

FEBS Lett. 2004 Jul 16;570(1-3):102-6. doi: 10.1016/j.febslet.2004.06.019.

Abstract

In the present study, we characterized hydrogen peroxide (H2O2)-induced cell apoptosis and related cell signaling pathways in cultured embryonic neural stem/progenitor cells (NS/PCs). Our data indicated that H2O2 induced acute cell apoptosis in NS/PC in concentration- and time-dependent manners and selectively, it transiently increased PI3K-Akt and Mek-Erk1/2 in a dose-dependent manner. Inhibition of PI3K-Akt with wortmannin, a PI3-K inhibitor, was found to significantly increase H2O2-induced acute apoptosis and dramatically decrease basal pGSK3beta levels. The level of pGSK3beta remained unchanged with H2O2 exposure. We conclude that the transient activation of PI3K-Akt signaling delays the H2O2-induced acute apoptosis in cultured NS/PCs in part through maintaining the basal pGSK3beta level and activating other downstream effectors.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Apoptosis*
  • Blotting, Western
  • Brain / embryology
  • Cell Death
  • DNA Fragmentation
  • Densitometry
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fluoresceins / metabolism
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hydrogen Peroxide / pharmacology*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / pathology*
  • Oxidative Stress
  • Phosphorylation
  • Propidium / pharmacology
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / pathology*
  • Time Factors
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Fluoresceins
  • Proto-Oncogene Proteins
  • Propidium
  • Hydrogen Peroxide
  • Akt1 protein, rat
  • Glycogen Synthase Kinase 3 beta
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Glycogen Synthase Kinase 3
  • fluorexon
  • Wortmannin